On September 6, 2022 NuCana plc (NASDAQ: NCNA) reported two presentations at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022 being held September 9-13, 2022 at the Paris Expo Porte de Versailles in Paris, France (Press release, Nucana BioPharmaceuticals, SEP 6, 2022, View Source [SID1234619024]).
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The details of NuCana’s presentations at ESMO (Free ESMO Whitepaper) are as follows:
Title: NUC-3373, a ProTide transformation of 5-FU, in combination with oxaliplatin (NUFOX) or irinotecan (NUFIRI) in patients with advanced colorectal cancer (CRC) (NuTide:302)
Abstract Number: 1752
Presentation: 345P
Presentation Date & Time: Sunday, September 11, 2022 at 9:00 a.m. CEST
Location: Hall 4 and the virtual Congress platform
Presenting Author: Andrew L. Coveler
Title: NUC-7738 in patients with advanced solid tumours: Phase I results from the NuTide:701 phase I/2 study
Abstract Number: 4992
Presentation: 455MO
Presentation Date & Time: Monday, September 12, 2022 at 4:30 p.m. CEST
Location: Toulouse Auditorium
Presenting Author: Stefan N. Symeonides
About NUC-3373
NUC-3373 is a phosphoramidate transformation of 5-fluorouracil, or 5-FU, which is designed to overcome the key limitations and pharmacologic challenges that hinder the clinical utility of 5-FU, with the aim of improving 5-FU’s efficacy, safety and administration challenges.
5-FU (and its other forms including capecitabine) is an inactive prodrug and its anti-cancer activity is dependent on its conversion to the active anti-cancer metabolite (FUDR-MP), which binds to and inhibits thymidylate synthase (TS), a critical enzyme in de novo nucleotide synthesis and cell survival. TS is required to convert uridine (specifically dUMP) to thymidine (specifically dTMP), one of the four nucleotides that comprise DNA. The inhibition of TS results in an imbalance in the ratio of dUMP and dTMP, thereby disrupting DNA synthesis and repair, ultimately leading to cancer cell death. However, due to multiple limitations, 5-FU is not efficiently converted to FUDR-MP.
NUC-3373 generates much higher concentrations of FUDR-MP in patients’ cells. It also has a more convenient administration schedule and does not produce toxic levels of metabolites such as FBAL or FUTP (which are associated with hand-foot syndrome, neutropenia, mucositis and diarrhea) resulting in an improved safety profile.
About NUC-7738
NUC-7738 is a phosphoramidate transformation of 3′-deoxyadenosine (3′-dA), also known as cordycepin. 3’-dA has demonstrated potent anti-cancer activity in non-clinical studies, but has not been successfully developed as an anti-cancer agent due to its rapid breakdown by adenosine deaminase (ADA). NUC-7738 is designed to generate the active anti-cancer metabolite of 3’-dA directly inside cancer cells, thus overcoming 3’-dA’s key limitations of breakdown, transportation and activation. The cytotoxic effect of NUC-7738 is largely attributed to the generation of the main active anti-cancer metabolite, 3′-dATP which interferes with RNA polyadenylation, causing changes in the expression of genes involved in various cellular processes, ultimately leading to cell death.